Comparative genomics of the class 4 histone deacetylase family indicates a complex evolutionary history

BACKGROUND: Histone deacetylases are enzymes that modify core histones and play key roles in transcriptional regulation, chromatin assembly, DNA repair, and recombination in eukaryotes. Three types of related histone deacetylases (classes 1, 2, and 4) are widely found in eukaryotes, and structurally related proteins have also been found in some prokaryotes. Here we focus on the evolutionary history of the class 4 histone deacetylase family. RESULTS: Through sequence similarity searches against sequenced genomes and expressed sequence tag data, we identified members of the class 4 histone deacetylase family in 45 eukaryotic and 37 eubacterial species representative of very distant evolutionary lineages. Multiple phylogenetic analyses indicate that the phylogeny of these proteins is, in many respects, at odds with the phylogeny of the species in which they are found. In addition, the eukaryotic members of the class 4 histone deacetylase family clearly display an anomalous phyletic distribution. CONCLUSION: The unexpected phylogenetic relationships within the class 4 histone deacetylase family and the anomalous phyletic distribution of these proteins within eukaryotes might be explained by two mechanisms: ancient gene duplication followed by differential gene losses and/or horizontal gene transfer. We discuss both possibilities in this report, and suggest that the evolutionary history of the class 4 histone deacetylase family may have been shaped by horizontal gene transfers.